Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype ...Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype or develop resistance to therapeutic interventions,leading to tumor metastasis and a poorer prognosis.When PC metastasizes to distant sites,the bone remains the predominant location,and brain metastases are regarded as exceedingly rare.Case Description:The current study focused on a rare clinical PC case that presented multiple brain metastases after prostate surgery.The patient was initially diagnosed with PC through prostate biopsy and subsequently underwent prostate debulking surgery while continuing androgen deprivation therapy,which maintained low prostatespecific antigen(PSA)levels for 4 years.However,a sudden PSA surge to 7.858 ng/mL led to the emergence of two brain metastatic tumors,which were confirmed to have originated from the prostate.Conclusions:Patients with advanced PC require comprehensive evaluations to detect rare metastatic sites,such as the brain,to avoid missed diagnoses.For patients with brain metastases,a multimodal approach combining surgical resection,postoperative radiotherapy,and endocrine therapy can effectively alleviate symptoms and enhance survival.展开更多
Background:Low-dose rate(LDR)prostate brachytherapy is a recommended treatment of localized prostate cancer in current guidelines.The study aimed to determine biochemical relapse-free survival(BRFS)in patients treated...Background:Low-dose rate(LDR)prostate brachytherapy is a recommended treatment of localized prostate cancer in current guidelines.The study aimed to determine biochemical relapse-free survival(BRFS)in patients treated with dynamic real-time low-dose rate(LDR)brachytherapy using Iodine 125(I^(125)).Methods:We retrospectively reviewed 499 patients with localized prostate cancer treated with I^(125) LDR realtime brachytherapy between 2003 and 2021.The mean patient age was 65 years(range:45–84 years).Based on the National Comprehensive Cancer Network(NCCN)risk classification,230 patients(46.1%)were categorized as low risk,235(47.1%)as intermediate risk,and 34(6.8%)as high risk.Gleason scores were distributed as follows:3+3 in 283 cases(56.7%),3+4 in 157 cases(31.5%),4+3 in 46 cases(9.2%),and 4+4 in 13 cases(2.6%).The mean follow-up was 70.5 months.Results:Tumor relapse was observed in 47 patients(9.4%)over a mean follow-up period of 6.26 years(SD 4.16).Local recurrence within the prostate occurred in 20 cases(4%).Patients with nadir PSA<0.2 ng/mL at 5 years of follow-up had a significantly lower incidence of tumor recurrence(3%)compared to those with a nadir PSA>0.2 ng/mL(21.9%)(p=0.0001).Biochemical relapse-free(BRFS)rates at 5,10 and 15 years were 96%,91.5% and 88.9%,respectively.When stratified by NCCCN risk groups,5-year BRFS was 96% in low risk,98% in intermediate risk and 85% in high risk patients(p=0.003).Inmultivariate analysis,only age at the time of brachytherapy(p=0.009),initial PSA(p=0.007)and Gleason grade(p=0.007)were significantly associated with tumor recurrence.Cancer-specific survival and overall survival were 99.8% and 98.0%,respectively.Conclusions:LDR with I^(125) has excellent longterm oncological outcomes for patients with low and intermediate-risk prostate cancer,in particular,patients achieving a nadir PSA<0.2 ng/mL at 5 years post-treatment.展开更多
Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(P...Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.展开更多
Objectives:PSMA PET/CT(Prostate-Specific MembraneAntigen Positron Emission Tomography/Computed Tomography)offers improved accuracy in detecting lymph node invasion(LNI)in prostate cancer(PC)patients,potentially reduci...Objectives:PSMA PET/CT(Prostate-Specific MembraneAntigen Positron Emission Tomography/Computed Tomography)offers improved accuracy in detecting lymph node invasion(LNI)in prostate cancer(PC)patients,potentially reducing the need for extended pelvic lymph node dissection(ePLND).This study aims to evaluate a patient-tailored care pathway in which ePLND is performed only in patients with unfavorable intermediate-or high-risk PC who are deemed at risk for LNI based on PSMA PET/CT findings.Methods:In this interventional cohort study,81 patients were managed according to the new care pathway.ePLND was omitted in cases of negative PSMA PET/CT findings(N0M0),while those with positive PSMA PET/CT findings(N1M0)underwent ePLND.A comparator group of 81 patients was selected from a prospectively generated database for comparison.Results:The intervention group experienced a 75% reduction in the number of ePLNDs performed compared to the comparator group(p<0.001).ePLND-related complications were significantly lower in the intervention group(p=0.008).No significant difference was observed in 3-year biochemical-recurrence free survival(BRFS)between the two groups(p=0.958).Conclusion:Omitting ePLND in patients with negative PSMA PET/CT findings(N0M0)leads to a substantial reduction in the number of ePLNDs performed,resulting in a decrease in morbidity,without compromising early oncological outcomes.展开更多
Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim ...Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.展开更多
Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly can...Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly cancer-associated fibroblasts(CAFs),as a critical determinant of disease behavior.CAFs constitute a heterogeneous population originating from fibroblasts,mesenchymal stem cells,endothelial cells,epithelial cells undergoing epithelial-mesenchymal transition(EMT),and adipose tissue.Through dynamic crosstalk with tumor,immune,endothelial,and adipocyte compartments,CAFs orchestrate oncogenic processes including tumor proliferation,invasion,immune evasion,extracellular matrix remodeling,angiogenesis,and metabolic reprogramming.This review comprehensively summarizes the cellular origins,phenotypic and functional heterogeneity,and spatial distribution of CAFs within the prostate TME.We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance,and critically evaluate emerging strategies to therapeutically target CAFmediated signaling,metabolic,and immune pathways.By integrating recent advances from single-cell and spatial transcriptomics(ST),our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.展开更多
Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated signi...Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.展开更多
Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isol...Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isolated from Helminthostachys zeylanica,on PCa metastasis.Methods:The effects of Ugonin J on cell motility were assessed using migration and invasion assays.Reverse Transcription Quantitative PCR(RT-qPCR)and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression.RNA sequencing(RNA-seq)analysis was performed to investigate candidate mechanisms.Differential gene expression analysis in PCa patients was conducted using multiple databases.Results:Here,we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability.RNA-seq analysis suggests that epithelial-mesenchymal transition(EMT)is potentially involved in Ugonin J’s anti-motility effects.Ugonin J also suppresses the expression of mesenchymal markers N-cadherin,β-catenin,Snail,and Slug while upregulating the expression of the epithelial marker E-cadherin.Furthermore,among 13 A disintegrin and metalloproteinase(ADAM)proteins,A disintegrin and metalloproteinase domain-containing protein 9(ADAM9)is the most downregulated following Ugonin J treatment,according to our RNA-seq data.Importantly,clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis.Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT,migration,and invasion in PCa cells.Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase(PI3K),protein kinase B(Akt)and nuclear factor-κB(NF-κB)pathways.Conclusions:Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.展开更多
Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with near...Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with nearly 400,000 associated deaths1. Notably, the incidence of PC in China has increased substantially compared to the global average2.展开更多
BACKGROUND Vitamin D deficiency has been associated with prostate cancer,particularly in ethnic minorities.Patients with prostate cancer may still be deficient even in areas of high sun exposure.Although androgen depr...BACKGROUND Vitamin D deficiency has been associated with prostate cancer,particularly in ethnic minorities.Patients with prostate cancer may still be deficient even in areas of high sun exposure.Although androgen deprivation therapy(ADT)is well documented to affect bone health,its impact on vitamin D levels is still uncertain.This study investigates the subgroups of prostate cancer patients most associated with vitamin D deficiency and ADT’s relation to this.AIM To examine how prevalent vitamin D deficiency is among prostate cancer patients in a sun-rich environment,with focus on differences by race and disease stage.It also assessed whether ADT is associated with changes in vitamin D levels.METHODS Prostate cancer patients treated at Chao Family Comprehensive Cancer Center between 2014-2024 were retrospectively studied with regards to vitamin D levels across racial groups,disease stages,and ADT exposure.Changes in vitamin D levels pre-and post-ADT over 24 months were assessed by statistical methods including paired t-tests.RESULTS Among 120 patients(mean age:74 years,mean body mass index:27.6 kg/m^(2)),African American(33.3%)and Hispanic(31.8%)patients had the greatest prevalence of vitamin D deficiency(<20 ng/mL).With a 28.6%deficit rate,metastatic castration-resistant prostate cancer had the highest prevalence rates of deficiency.There was no significant difference between pre-and post-ADT vitamin D levels(P=0.45).CONCLUSION Vitamin D deficiency is common in prostate cancer patients,especially racial minorities and those with advanced disease,despite residing in an area with high sun exposure.ADT does not significantly impact vitamin D levels in the short term.Routine screening and supplementation should be considered in these high-risk groups.展开更多
In recent years,advancements in single-cell and spatial transcriptomics,which are highly regarded developments in the current era,particularly the emerging integration of single-cell and spatiotemporal transcriptomics...In recent years,advancements in single-cell and spatial transcriptomics,which are highly regarded developments in the current era,particularly the emerging integration of single-cell and spatiotemporal transcriptomics,have enabled a detailed molecular comprehension of the complex regulation of cell fate.The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine.Currently,single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors.Start-ing from the perspective of RNA sequencing technology,this review outlined the signifcance of single-cell RNA sequencing(scRNA-seq)in prostate cancer research,encompassing preclinical medicine and clinical applications.We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies,as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis,treatment,and drug resistance characteristics of prostate cancer.These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer.Furthermore,we explore the potential clinical applications stemming from other single-cell technologies in this review,paving the way for future research in precision medicine.展开更多
Background:Transmembrane emp24 trafficking protein 3(TMED3)is associated with the development of several tumors;however,whether TMED3 regulates the progression of prostate cancer remains unclear.Materials and Methods:...Background:Transmembrane emp24 trafficking protein 3(TMED3)is associated with the development of several tumors;however,whether TMED3 regulates the progression of prostate cancer remains unclear.Materials and Methods:Short hairpin RNA was performed to repress TMED3 in prostate cancer cells(DU145 cells)and in a prostate cancer mice model to determine its function in prostate cancer in vitro and in vivo.Results:In the present study,we found that TMED3 was highly expressed in prostate cancer cells.In vitro,shTMED3 treatment suppressed the proliferation,invasion,and migration and promoted the apoptosis of DU145 cells.Additionally,the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed a strong correlation between TMED3 and forkhead box O transcription factor(FOXO)pathway.Furthermore,TMED3 inhibition efficiently decreased FOXO1a and FOXO3a phosphorylation.In vivo,TMED3 downregulation suppressed the apoptosis,growth,and metastasis of prostate cancer cells via FOXO1a and FOXO3a.Conclusion:The present findings show that TMED3 participates in the regulation of prostate cancer progression via FOXO1a and FOXO3a phosphorylation,thereby revealing a novel mechanism underlying prostate cancer development and suggesting that TMED3 inhibition may serve as a novel strategy for prostate cancer treatment.展开更多
Prostate cancer(PCa)is one of the most common malignant tumors in the male genitourinary system,ranking second in incidence worldwide.Traditional Chinese medicine(TCM),as an important component of complementary and al...Prostate cancer(PCa)is one of the most common malignant tumors in the male genitourinary system,ranking second in incidence worldwide.Traditional Chinese medicine(TCM),as an important component of complementary and alternative medicine,shows unique advantages in cancer treatment.Chinese herbal medicine is usually composed of multiple ingredients and involves multiple signaling pathways,which showed function of inducing apoptosis of cancer cells,arresting the cell cycle,inhibiting invasion and metastasis,reducing drug resistance,and regulating immune function.Physical therapy is also an important treatment of TCM.Currently,Physical therapy such as acupuncture or Tai Chi and Qigong are gaining increased recognition in the management of PCa,particularly in addressing issues like urinary incontinence and bone metastasis-related pain.This article reviews the TCM treatment and therapy of PCa,in order to provide new research avenues and treatment options for the treatment of PCa with TCM and improve the quality of life of patients.展开更多
Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogenei...Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer.NEPC may arise de novo or develop following androgen deprivation therapy(ADT).NEPC that arise following ADT has the nomenclature“treatmentemerging/induced NEPC(t-NEPC)”.t-NEPC would be anticipated in castration resistant prostate cancer(CRPC)and metastatic PCa.t-NEPC is characterized by low or absent androgen receptor(AR)expression,independence of AR signaling,and gain of neuroendocrine phenotype.t-NEPC is an aggressive metastatic tumor,develops from PCa in response to drug induced ADT,and shows very short response to conventional therapy.t-NEPC occurs in 10%-17%of patients with CRPC.De novo NEPC is rare and is accounting for less than 2%of all PCa.The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated.Sphingosine kinase 1 plays a significant role in t-NEPC development.Although neuroendocrine markers:Synaptophysin,chromogranin A,and insulinoma associated protein 1(INSM1)are expressed in t-NEPC,they are non-specific for diagnosis,prognosis,and follow-up of therapy.t-NEPC shows enriched genomic alteration in tumor protein P53(TP53)and retinoblastoma 1(RB1).There are evidences suggest that t-NEPC might develop through epigenetic evolution.There are genomic,epigenetic,and transcriptional alterations that are reported to be involved in development of t-NEPC.Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC.PCa is resistant to immunotherapy,and at present there are running trials to approach immunotherapy for PCa,CRPC,and t-NEPC.展开更多
Objective:This review provides a comprehensive overview of the current research landscape on artificial intelligence(AI)in prostate cancer(PCa)management,highlighting its potential to enhance diagnosis,improve medical...Objective:This review provides a comprehensive overview of the current research landscape on artificial intelligence(AI)in prostate cancer(PCa)management,highlighting its potential to enhance diagnosis,improve medical image quality,facilitate risk stratification,and aid prognosis.The review also identifies opportunities and challenges associated with integrating AI into clinical practice.Methods:This review synthesizes findings from recent studies on AI applications in PCa management.It examines the use of machine learning and deep learning techniques in diagnostic imaging,surgical skill assessment,and outcome prediction.The analysis emphasizes empirical evidence demonstrating the efficacy and limitations of AI models in clinical settings.Results:AI,particularly machine learning and deep learning algorithms,is improving diagnostic accuracy by analyzing medical images with greater efficiency and precision compared to traditional methods.AI-based tools are also being developed for surgical skill assessment,offering objective evaluations and feedback to surgeons.Additionally,AI applications in predicting patient outcomes are facilitating the creation of personalized treatment plans.Empirical evidence shows that AI models exhibit higher sensitivity and specificity in detecting clinically significant PCa,outperforming conventional diagnostic techniques.Conclusion:AI holds significant promise for transforming PCa management by improving diagnostic accuracy,personalizing treatment plans,and enhancing patient outcomes.While the evidence underscores its potential,challenges such as the need for larger,more diverse datasets and addressing implementation barriers remain critical.Despite these hurdles,the benefits of AI in PCa management represent a compelling area for future research and clinical integration.展开更多
The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research...The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.展开更多
This article comprehensively reviews research progress in prostate cancer radiation therapy.It provides an overview of fundamental principles,encompassing the disease’s epidemiology,pathological mechanisms,and radiat...This article comprehensively reviews research progress in prostate cancer radiation therapy.It provides an overview of fundamental principles,encompassing the disease’s epidemiology,pathological mechanisms,and radiation sensitivity,alongside technological advancements.The clinical application,technological progress,and efficacy evaluation of moderate hypofractionated radiation therapy and ultra hypofractionated radiation therapy are discussed.Diagnostic and monitoring techniques specific to radiation therapy are analyzed,alongside prevailing controversies and challenges.Finally,the review outlines future prospects,including novel radiotherapy techniques,multidisciplinary collaboration trends,and the evolving role of radiation within comprehensive treatment.The findings demonstrate continuous technological and clinical evolution in prostate cancer radiotherapy,yet emphasize the need for further exploration to optimize treatments and improve patient survival and quality of life.展开更多
As a practicing anatomic pathologist specialized in urologic pathology,a vast difference may be observed between what pathologists designate as neuroendocrine(or small cell)carcinoma of the prostate,and what clinician...As a practicing anatomic pathologist specialized in urologic pathology,a vast difference may be observed between what pathologists designate as neuroendocrine(or small cell)carcinoma of the prostate,and what clinicians or basic scientists define as such.展开更多
Prostate cancer is a significant global health issue with inflammation emerging as a critical driver of progression.The prostate tumor microenvironment(TME)is comprised of tumor cells,mesenchymal stem cells,immune cel...Prostate cancer is a significant global health issue with inflammation emerging as a critical driver of progression.The prostate tumor microenvironment(TME)is comprised of tumor cells,mesenchymal stem cells,immune cells,cancer-associated fibroblasts,adipocytes,and the extracellular matrix.All of these TME components interact via soluble factors,such as growth factors,cytokines,and chemokines.These interactions remodel the TME and drive inflammation and tumor progression.Prolonged inflammation leads to dysregulated activation and infiltration of immune cells in the TME.This process maintains an immunosuppressive environment and facilitates epithelial-to-mesenchymal transition,migration,and invasion.Chronic inflammation causes inflammatory mediators to enter the circulation over time,as evidenced by systemic biomarkers,such as the systemic immune-inflammation index,which links inflammation to disease severity.Interactions between the prostate gland and adipose tissues further exacerbate systemic inflammation.Inflammation in the prostate gland confers resistance to therapy,primes distant metastatic niches,and promotes metastatic spread,resulting in poor clinical outcomes.Therapeutic strategies,such as anti-inflammatory agents and immunotherapies,hold promise in mitigating disease burden.This review explored the immune landscape of systemic inflammation in prostate cancer,discussed the role of the immune landscape in resistance to therapy and metastasis,and offered insights into potential interventions for targeting inflammation to limit prostate cancer burden.展开更多
Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regula...Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regulate gene transcription via nuclear receptors TRα/β,modulating proliferation,apoptosis,and AR signaling,while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K-Akt signaling,driving metabolic reprogramming,migration,and angiogenesis.Local DIO enzymes fine-tune T3/T4 levels,with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion.Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk,whereas experimental models show inconsistent effects,reflecting regulation by hormone levels,receptor distribution,and tumor molecular features.Bibliometric analyses reveal a shift from epidemiological studies to molecular,immune,and metabolic mechanistic research,though clinical translation remains limited.This review synthesizes current knowledge on THs in PCa,highlighting mechanistic insights,evidence gaps,and future directions,aiming to inform early detection,stratification,and therapeutic strategies.展开更多
基金supported by the National Natural Science Foundation[Grant Number:82102788]Anhui Province Key Project for Clinical Medical Research Translation and Advancement[202204295107020031,202204295107020007]Anhui Provincial University Excellent Scientific Research and Innovation Team Project[2022AH010071].
文摘Background:In clinical practice,approximately 80%of prostate cancer(PC)cases are localized and can achieve favorable outcomes with appropriate treatment.Conversely,some remaining cases exhibit an aggressive phenotype or develop resistance to therapeutic interventions,leading to tumor metastasis and a poorer prognosis.When PC metastasizes to distant sites,the bone remains the predominant location,and brain metastases are regarded as exceedingly rare.Case Description:The current study focused on a rare clinical PC case that presented multiple brain metastases after prostate surgery.The patient was initially diagnosed with PC through prostate biopsy and subsequently underwent prostate debulking surgery while continuing androgen deprivation therapy,which maintained low prostatespecific antigen(PSA)levels for 4 years.However,a sudden PSA surge to 7.858 ng/mL led to the emergence of two brain metastatic tumors,which were confirmed to have originated from the prostate.Conclusions:Patients with advanced PC require comprehensive evaluations to detect rare metastatic sites,such as the brain,to avoid missed diagnoses.For patients with brain metastases,a multimodal approach combining surgical resection,postoperative radiotherapy,and endocrine therapy can effectively alleviate symptoms and enhance survival.
文摘Background:Low-dose rate(LDR)prostate brachytherapy is a recommended treatment of localized prostate cancer in current guidelines.The study aimed to determine biochemical relapse-free survival(BRFS)in patients treated with dynamic real-time low-dose rate(LDR)brachytherapy using Iodine 125(I^(125)).Methods:We retrospectively reviewed 499 patients with localized prostate cancer treated with I^(125) LDR realtime brachytherapy between 2003 and 2021.The mean patient age was 65 years(range:45–84 years).Based on the National Comprehensive Cancer Network(NCCN)risk classification,230 patients(46.1%)were categorized as low risk,235(47.1%)as intermediate risk,and 34(6.8%)as high risk.Gleason scores were distributed as follows:3+3 in 283 cases(56.7%),3+4 in 157 cases(31.5%),4+3 in 46 cases(9.2%),and 4+4 in 13 cases(2.6%).The mean follow-up was 70.5 months.Results:Tumor relapse was observed in 47 patients(9.4%)over a mean follow-up period of 6.26 years(SD 4.16).Local recurrence within the prostate occurred in 20 cases(4%).Patients with nadir PSA<0.2 ng/mL at 5 years of follow-up had a significantly lower incidence of tumor recurrence(3%)compared to those with a nadir PSA>0.2 ng/mL(21.9%)(p=0.0001).Biochemical relapse-free(BRFS)rates at 5,10 and 15 years were 96%,91.5% and 88.9%,respectively.When stratified by NCCCN risk groups,5-year BRFS was 96% in low risk,98% in intermediate risk and 85% in high risk patients(p=0.003).Inmultivariate analysis,only age at the time of brachytherapy(p=0.009),initial PSA(p=0.007)and Gleason grade(p=0.007)were significantly associated with tumor recurrence.Cancer-specific survival and overall survival were 99.8% and 98.0%,respectively.Conclusions:LDR with I^(125) has excellent longterm oncological outcomes for patients with low and intermediate-risk prostate cancer,in particular,patients achieving a nadir PSA<0.2 ng/mL at 5 years post-treatment.
基金supported by Tianjian advanced biomedical laboratory key research and development projectHenan Province Natural Science Foundation(Grant Number 242300421283)Major Science and Technology Project of Henan Province(221100310200)。
文摘Background:The gut microbiome has emerged as a critical modulator of cancer immunotherapy response.However,the mechanisms by which gut-associated metabolites influence checkpoint blockade efficacy in prostate cancer(PC)remain not fully explored.The study aimed to explore how gut metabolites regulate death-ligand 1(PD-L1)blockade via exosomes and boost immune checkpoint inhibitors(ICIs)in PC.Methods:We recruited 70 PC patients to set up into five subgroups.The integrated multi-omics analysis was performed.In parallel,we validated the function of gut microbiome-associated metabolites on PD-L1 production and immunotherapy treatment efficacy in PC cell lines and transgenic adenocarcinoma of the mouse prostate(TRAMP)models.Results:We identified two metabolites,16(R)-Hydroxyeicosatetraenoic acid(16(R)-HETE)and 6-Keto-Prostaglandin E1(6-Keto-PGE1),that positively correlated with the plasma exosomal PD-L1 levels.The in vitro experiments found that both 16(R)-HETE and 6-Keto-PGE1 can enhance PD-L1 expression at the mRNA,protein,and exosome levels in both human and mouse PC cell lines,which were also validated in vivo based on subcutaneous mouse models.Both metabolites significantly promoted the anti-PD-L1 efficacy against PC in situ on a TRAMP mouse model.Conclusions:Targeting the“gut-tumor metabolic axis”is a promising strategy to improve the efficacy of immune checkpoint inhibitors in tumors.
基金supported by a grant from Kom op tegen Kanker(Stand Up to Cancer,Belgium).
文摘Objectives:PSMA PET/CT(Prostate-Specific MembraneAntigen Positron Emission Tomography/Computed Tomography)offers improved accuracy in detecting lymph node invasion(LNI)in prostate cancer(PC)patients,potentially reducing the need for extended pelvic lymph node dissection(ePLND).This study aims to evaluate a patient-tailored care pathway in which ePLND is performed only in patients with unfavorable intermediate-or high-risk PC who are deemed at risk for LNI based on PSMA PET/CT findings.Methods:In this interventional cohort study,81 patients were managed according to the new care pathway.ePLND was omitted in cases of negative PSMA PET/CT findings(N0M0),while those with positive PSMA PET/CT findings(N1M0)underwent ePLND.A comparator group of 81 patients was selected from a prospectively generated database for comparison.Results:The intervention group experienced a 75% reduction in the number of ePLNDs performed compared to the comparator group(p<0.001).ePLND-related complications were significantly lower in the intervention group(p=0.008).No significant difference was observed in 3-year biochemical-recurrence free survival(BRFS)between the two groups(p=0.958).Conclusion:Omitting ePLND in patients with negative PSMA PET/CT findings(N0M0)leads to a substantial reduction in the number of ePLNDs performed,resulting in a decrease in morbidity,without compromising early oncological outcomes.
文摘Poly-and perfluoroalkyl substances(PFAS),including perfluorooctanoic acid(PFOA)and perfluorooctane sul-fonate(PFOS),are persistent environmental pollutants with potential toxicological effects on human health.The aim of this study was to investigate the impact of PFOS and PFOA on the effectiveness of selected drugs used in the treatment of prostate cancer based on in vitro tests on cell lines.Three cell lines were used in the study:two human prostate cancer cells(DU-145 and PC3)and one human normal prostate cell line(PNT1A).Using dose-response experiments,it was observed that PFAS had differential effects on cancer and normal cells.At low concentrations,PFOA and PFOS stimulated the proliferation of cancer cells,particularly PC3,while higher concentrations led to reduced viability.In normal cells,PFOS exhibited greater cytotoxicity compared to PFOA.Furthermore,PFOS enhanced docetaxel cytotoxicity in PC3 cells but reduced its efficacy in DU-145 cells.Similarly,PFOA diminished cabazitaxel effectiveness in DU-145 cells,suggesting PFAS-drug interactions may depend on the cell type,drug,and PFAS concentration.Results suggest that PFAS may influence cellular processes through receptor-mediated pathways,oxidative stress modulation,and protein binding,altering drug bioavailability and cellular uptake.The study also highlights the non-monotonic dose-response relationships observed in PFAS-treated cells.These findings raise concerns about the potential risks associated with PFAS exposure,particularly in the context of cancer treatment.Future studies should focus on long-term,low-dose PFAS exposure,the use of primary cells,and the molecular mechanisms driving these interactions to better inform therapeutic strategies.
文摘Prostate cancer(PCa)remains a major cause of cancer-related mortality in men,largely due to therapy resistance and metastatic progression.Increasing evidence highlights the tumor microenvironment(TME),particularly cancer-associated fibroblasts(CAFs),as a critical determinant of disease behavior.CAFs constitute a heterogeneous population originating from fibroblasts,mesenchymal stem cells,endothelial cells,epithelial cells undergoing epithelial-mesenchymal transition(EMT),and adipose tissue.Through dynamic crosstalk with tumor,immune,endothelial,and adipocyte compartments,CAFs orchestrate oncogenic processes including tumor proliferation,invasion,immune evasion,extracellular matrix remodeling,angiogenesis,and metabolic reprogramming.This review comprehensively summarizes the cellular origins,phenotypic and functional heterogeneity,and spatial distribution of CAFs within the prostate TME.We further elucidate the molecular mechanisms by which CAFs regulate PCa progression and therapeutic resistance,and critically evaluate emerging strategies to therapeutically target CAFmediated signaling,metabolic,and immune pathways.By integrating recent advances from single-cell and spatial transcriptomics(ST),our objective is to provide a holistic framework for understanding CAF biology and to highlight potential avenues for stromal reprogramming as an adjunct to current PCa therapies.
文摘Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.
基金supported by the National Science and Technology Council(NSTC 113-2320-B-039-049-MY3 and NSTC 114-2314-B-039-051-MY3)China Medical University(CMU113-ASIA-05,CMU-114-ASIA-01).
文摘Background:Prostate cancer(PCa)is the most prevalent malignancy in men and often correlates with distant metastasis in its advanced stages.The study aimed to investigate the effects of Ugonin J,a natural compound isolated from Helminthostachys zeylanica,on PCa metastasis.Methods:The effects of Ugonin J on cell motility were assessed using migration and invasion assays.Reverse Transcription Quantitative PCR(RT-qPCR)and Western blotting were used to evaluate the impact of Ugonin J on mRNA and protein expression.RNA sequencing(RNA-seq)analysis was performed to investigate candidate mechanisms.Differential gene expression analysis in PCa patients was conducted using multiple databases.Results:Here,we reveal that Ugonin J blocks migration and invasion in PCa cells without affecting cell viability.RNA-seq analysis suggests that epithelial-mesenchymal transition(EMT)is potentially involved in Ugonin J’s anti-motility effects.Ugonin J also suppresses the expression of mesenchymal markers N-cadherin,β-catenin,Snail,and Slug while upregulating the expression of the epithelial marker E-cadherin.Furthermore,among 13 A disintegrin and metalloproteinase(ADAM)proteins,A disintegrin and metalloproteinase domain-containing protein 9(ADAM9)is the most downregulated following Ugonin J treatment,according to our RNA-seq data.Importantly,clinical data revealed that ADAM9 expression are higher in PCa patients than in healthy controls and are associated with distant metastasis.Transfection with ADAM9 cDNA reverses Ugonin J-regulated downregulation of EMT,migration,and invasion in PCa cells.Ugonin J inhibits ADAM9-dependent motility by downregulating the phosphoinositide 3-kinase(PI3K),protein kinase B(Akt)and nuclear factor-κB(NF-κB)pathways.Conclusions:Our evidence suggests that Ugonin J is a novel therapeutic candidate for further development as a treatment for metastatic PCa.
文摘Prostate cancer (PC) is among the most common cancer diagnoses in men worldwide and the fifth leading cause of cancer-related deaths. Approximately 1.5 million new cases of PC were reported worldwide in 2022 with nearly 400,000 associated deaths1. Notably, the incidence of PC in China has increased substantially compared to the global average2.
文摘BACKGROUND Vitamin D deficiency has been associated with prostate cancer,particularly in ethnic minorities.Patients with prostate cancer may still be deficient even in areas of high sun exposure.Although androgen deprivation therapy(ADT)is well documented to affect bone health,its impact on vitamin D levels is still uncertain.This study investigates the subgroups of prostate cancer patients most associated with vitamin D deficiency and ADT’s relation to this.AIM To examine how prevalent vitamin D deficiency is among prostate cancer patients in a sun-rich environment,with focus on differences by race and disease stage.It also assessed whether ADT is associated with changes in vitamin D levels.METHODS Prostate cancer patients treated at Chao Family Comprehensive Cancer Center between 2014-2024 were retrospectively studied with regards to vitamin D levels across racial groups,disease stages,and ADT exposure.Changes in vitamin D levels pre-and post-ADT over 24 months were assessed by statistical methods including paired t-tests.RESULTS Among 120 patients(mean age:74 years,mean body mass index:27.6 kg/m^(2)),African American(33.3%)and Hispanic(31.8%)patients had the greatest prevalence of vitamin D deficiency(<20 ng/mL).With a 28.6%deficit rate,metastatic castration-resistant prostate cancer had the highest prevalence rates of deficiency.There was no significant difference between pre-and post-ADT vitamin D levels(P=0.45).CONCLUSION Vitamin D deficiency is common in prostate cancer patients,especially racial minorities and those with advanced disease,despite residing in an area with high sun exposure.ADT does not significantly impact vitamin D levels in the short term.Routine screening and supplementation should be considered in these high-risk groups.
基金Chinese Scholarship Council(202206240086)National Natural Science Foundation of China(81974099,82170785,81974098,82170784)+4 种基金National Key Research and Development Program of China(2021YFC2009303)programs from Science and Technology Department of Sichuan Province(2021YFH0172)Young Investigator Award of Sichuan University 2017(2017SCU04A17)Technology Innovation Research and Development Project of Chengdu Science and Technology Bureau(2019-YF05-00296-SN)Sichuan University-Panzhihua science and technology cooperation special fund(2020CDPZH-4).
文摘In recent years,advancements in single-cell and spatial transcriptomics,which are highly regarded developments in the current era,particularly the emerging integration of single-cell and spatiotemporal transcriptomics,have enabled a detailed molecular comprehension of the complex regulation of cell fate.The insights obtained from these methodologies are anticipated to significantly contribute to the development of personalized medicine.Currently,single-cell technology is less frequently utilized for prostate cancer compared with other types of tumors.Start-ing from the perspective of RNA sequencing technology,this review outlined the signifcance of single-cell RNA sequencing(scRNA-seq)in prostate cancer research,encompassing preclinical medicine and clinical applications.We summarize the differences between mouse and human prostate cancer as revealed by scRNA-seq studies,as well as a combination of multi-omics methods involving scRNA-seq to highlight the key molecular targets for the diagnosis,treatment,and drug resistance characteristics of prostate cancer.These studies are expected to provide novel insights for the development of immunotherapy and other innovative treatment strategies for castration-resistant prostate cancer.Furthermore,we explore the potential clinical applications stemming from other single-cell technologies in this review,paving the way for future research in precision medicine.
基金supported by Guangxi Medical and Health Appropriate Technology Development and Promotion Application Project(S2022022).
文摘Background:Transmembrane emp24 trafficking protein 3(TMED3)is associated with the development of several tumors;however,whether TMED3 regulates the progression of prostate cancer remains unclear.Materials and Methods:Short hairpin RNA was performed to repress TMED3 in prostate cancer cells(DU145 cells)and in a prostate cancer mice model to determine its function in prostate cancer in vitro and in vivo.Results:In the present study,we found that TMED3 was highly expressed in prostate cancer cells.In vitro,shTMED3 treatment suppressed the proliferation,invasion,and migration and promoted the apoptosis of DU145 cells.Additionally,the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed a strong correlation between TMED3 and forkhead box O transcription factor(FOXO)pathway.Furthermore,TMED3 inhibition efficiently decreased FOXO1a and FOXO3a phosphorylation.In vivo,TMED3 downregulation suppressed the apoptosis,growth,and metastasis of prostate cancer cells via FOXO1a and FOXO3a.Conclusion:The present findings show that TMED3 participates in the regulation of prostate cancer progression via FOXO1a and FOXO3a phosphorylation,thereby revealing a novel mechanism underlying prostate cancer development and suggesting that TMED3 inhibition may serve as a novel strategy for prostate cancer treatment.
基金supported by China Postdoctoral Science Foundation(2022M722674)Peixian Science and Technology Plan Project(P202410)Xuzhou Medical Reserve Talents Project(XWRCHT20220009).
文摘Prostate cancer(PCa)is one of the most common malignant tumors in the male genitourinary system,ranking second in incidence worldwide.Traditional Chinese medicine(TCM),as an important component of complementary and alternative medicine,shows unique advantages in cancer treatment.Chinese herbal medicine is usually composed of multiple ingredients and involves multiple signaling pathways,which showed function of inducing apoptosis of cancer cells,arresting the cell cycle,inhibiting invasion and metastasis,reducing drug resistance,and regulating immune function.Physical therapy is also an important treatment of TCM.Currently,Physical therapy such as acupuncture or Tai Chi and Qigong are gaining increased recognition in the management of PCa,particularly in addressing issues like urinary incontinence and bone metastasis-related pain.This article reviews the TCM treatment and therapy of PCa,in order to provide new research avenues and treatment options for the treatment of PCa with TCM and improve the quality of life of patients.
文摘Neuroendocrine prostate cancer(NEPC)shows an aggressive behavior compared to prostate cancer(PCa),also known as prostate adenocarcinoma.Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer.NEPC may arise de novo or develop following androgen deprivation therapy(ADT).NEPC that arise following ADT has the nomenclature“treatmentemerging/induced NEPC(t-NEPC)”.t-NEPC would be anticipated in castration resistant prostate cancer(CRPC)and metastatic PCa.t-NEPC is characterized by low or absent androgen receptor(AR)expression,independence of AR signaling,and gain of neuroendocrine phenotype.t-NEPC is an aggressive metastatic tumor,develops from PCa in response to drug induced ADT,and shows very short response to conventional therapy.t-NEPC occurs in 10%-17%of patients with CRPC.De novo NEPC is rare and is accounting for less than 2%of all PCa.The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated.Sphingosine kinase 1 plays a significant role in t-NEPC development.Although neuroendocrine markers:Synaptophysin,chromogranin A,and insulinoma associated protein 1(INSM1)are expressed in t-NEPC,they are non-specific for diagnosis,prognosis,and follow-up of therapy.t-NEPC shows enriched genomic alteration in tumor protein P53(TP53)and retinoblastoma 1(RB1).There are evidences suggest that t-NEPC might develop through epigenetic evolution.There are genomic,epigenetic,and transcriptional alterations that are reported to be involved in development of t-NEPC.Knock-outs of TP53 and RB1 were found to contribute in development of t-NEPC.PCa is resistant to immunotherapy,and at present there are running trials to approach immunotherapy for PCa,CRPC,and t-NEPC.
基金partly funded by the NIH/NCI Cancer Center Support Grant under grant No.P30 CA008748(MSK).
文摘Objective:This review provides a comprehensive overview of the current research landscape on artificial intelligence(AI)in prostate cancer(PCa)management,highlighting its potential to enhance diagnosis,improve medical image quality,facilitate risk stratification,and aid prognosis.The review also identifies opportunities and challenges associated with integrating AI into clinical practice.Methods:This review synthesizes findings from recent studies on AI applications in PCa management.It examines the use of machine learning and deep learning techniques in diagnostic imaging,surgical skill assessment,and outcome prediction.The analysis emphasizes empirical evidence demonstrating the efficacy and limitations of AI models in clinical settings.Results:AI,particularly machine learning and deep learning algorithms,is improving diagnostic accuracy by analyzing medical images with greater efficiency and precision compared to traditional methods.AI-based tools are also being developed for surgical skill assessment,offering objective evaluations and feedback to surgeons.Additionally,AI applications in predicting patient outcomes are facilitating the creation of personalized treatment plans.Empirical evidence shows that AI models exhibit higher sensitivity and specificity in detecting clinically significant PCa,outperforming conventional diagnostic techniques.Conclusion:AI holds significant promise for transforming PCa management by improving diagnostic accuracy,personalizing treatment plans,and enhancing patient outcomes.While the evidence underscores its potential,challenges such as the need for larger,more diverse datasets and addressing implementation barriers remain critical.Despite these hurdles,the benefits of AI in PCa management represent a compelling area for future research and clinical integration.
文摘The published article titled“Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway”has been retracted from Oncology Research,Vol.26,No.1,2018,pp.131–143.
文摘This article comprehensively reviews research progress in prostate cancer radiation therapy.It provides an overview of fundamental principles,encompassing the disease’s epidemiology,pathological mechanisms,and radiation sensitivity,alongside technological advancements.The clinical application,technological progress,and efficacy evaluation of moderate hypofractionated radiation therapy and ultra hypofractionated radiation therapy are discussed.Diagnostic and monitoring techniques specific to radiation therapy are analyzed,alongside prevailing controversies and challenges.Finally,the review outlines future prospects,including novel radiotherapy techniques,multidisciplinary collaboration trends,and the evolving role of radiation within comprehensive treatment.The findings demonstrate continuous technological and clinical evolution in prostate cancer radiotherapy,yet emphasize the need for further exploration to optimize treatments and improve patient survival and quality of life.
文摘As a practicing anatomic pathologist specialized in urologic pathology,a vast difference may be observed between what pathologists designate as neuroendocrine(or small cell)carcinoma of the prostate,and what clinicians or basic scientists define as such.
文摘Prostate cancer is a significant global health issue with inflammation emerging as a critical driver of progression.The prostate tumor microenvironment(TME)is comprised of tumor cells,mesenchymal stem cells,immune cells,cancer-associated fibroblasts,adipocytes,and the extracellular matrix.All of these TME components interact via soluble factors,such as growth factors,cytokines,and chemokines.These interactions remodel the TME and drive inflammation and tumor progression.Prolonged inflammation leads to dysregulated activation and infiltration of immune cells in the TME.This process maintains an immunosuppressive environment and facilitates epithelial-to-mesenchymal transition,migration,and invasion.Chronic inflammation causes inflammatory mediators to enter the circulation over time,as evidenced by systemic biomarkers,such as the systemic immune-inflammation index,which links inflammation to disease severity.Interactions between the prostate gland and adipose tissues further exacerbate systemic inflammation.Inflammation in the prostate gland confers resistance to therapy,primes distant metastatic niches,and promotes metastatic spread,resulting in poor clinical outcomes.Therapeutic strategies,such as anti-inflammatory agents and immunotherapies,hold promise in mitigating disease burden.This review explored the immune landscape of systemic inflammation in prostate cancer,discussed the role of the immune landscape in resistance to therapy and metastasis,and offered insights into potential interventions for targeting inflammation to limit prostate cancer burden.
基金Guangzhou Medical and Health Science and Technology Project(Project No.:20231A011103)General projects of Guangzhou municipal Science and Technology Bureau(Project No.:2023A04J0598)Guangdong Basic and Applied Basic Research Foundation(Project No.:2022A1515111122)。
文摘Prostate cancer(PCa)is a prevalent malignancy in men,traditionally linked to androgen receptor signaling.Emerging evidence suggests thyroid hormones(THs,particularly T3/T4)play a complex role in PCa biology.THs regulate gene transcription via nuclear receptors TRα/β,modulating proliferation,apoptosis,and AR signaling,while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K-Akt signaling,driving metabolic reprogramming,migration,and angiogenesis.Local DIO enzymes fine-tune T3/T4 levels,with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion.Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk,whereas experimental models show inconsistent effects,reflecting regulation by hormone levels,receptor distribution,and tumor molecular features.Bibliometric analyses reveal a shift from epidemiological studies to molecular,immune,and metabolic mechanistic research,though clinical translation remains limited.This review synthesizes current knowledge on THs in PCa,highlighting mechanistic insights,evidence gaps,and future directions,aiming to inform early detection,stratification,and therapeutic strategies.
